核因子κB受体活化因子配体和肿瘤坏死因子α经炎性牙周膜干细胞外泌体促进破骨细胞分化

目的　慢性牙周炎表现的病理性骨吸收非常常见，牙周膜干细胞（PDLSCs）的外泌体（Exo）对骨吸收的作用和影响尚不明确，本研究分析了该Exo蛋白组分对破骨细胞分化的影响。方法　分别从正畸前拔牙患者和慢性牙周炎患者的牙周膜组织中提取PDLSCs，通过流式细胞术检测表面标记物；通过差速离心分别提取2种细胞的Exo，即Exo-WT和Exo-CP，并通过Western blot、透射电子显微镜（TEM）、蛋白浓度检测、纳米粒径追踪检测Exo特征；通过蛋白质谱检测2种Exo的蛋白组分；通过酶联免疫吸附（ELISA）验证了差异表达蛋白肿瘤坏死因子α（TNF-α）、核因子κB受体活化因子配体（RANKL）、白细胞介素（IL）-1α、转化生长因子β（TGF-β）、骨形态发生蛋白2（BMP-2）表达水平；将10、100、1 000 μg·mL^-1的Exo-CP或Exo-WT加入RAW264.7培养基中并于5 d时通过实时荧光定量聚合酶链反应（RT-qPCR）、Western blot、抗酒石酸酸性磷酸酶（TRAP）染色检测破骨分化相关指标表达情况；采用SPSS 24.0软件对实验数据进行统计学分析。结果　Exo-CP富集的差异表达蛋白主要与破骨细胞分化的TNF信号通路、核转录因子κB（NF-κB）信号通路相关；ELISA实验证实了Exo-CP中高表达TNF-α、RANKL、IL-1α，低表达TGF-β1、BMP-2（P<0.05）；Exo-CP作用于RAW264.7，显著提高了细胞的破骨分化相关基因及蛋白的表达水平，TRAP染色可见分化的破骨细胞，且呈现浓度依赖性，100、1 000 μg·mL^-1浓度Exo-CP对破骨细胞分化的促进作用显著高于10 μg·mL^-1浓度组（P<0.05）。结论　慢性牙周炎的病理性骨吸收可能由炎性PDLSCs所分泌的Exo通过促进破骨细胞分化引起，Exo中主要的作用蛋白可能为RANKL和TNF-α，本研究为慢性牙周炎骨吸收的发病机制提供了新视角。     

Methodological advances in the design of peptide-based vaccines

The tremendous advances in genomics, recombinant DNA technology, bioengineering and nanotechnology, in conjunction with the development of high-end computations, have been instrumental in the process of rational design of peptide-based vaccines. The use of peptide vaccines was limited owing to their inherent instability when systemically administered; however, advanced formulation techniques have been developed for their systemic delivery, thereby overcoming their degradation, clearance, cellular uptake and off-target effects. With the rise of sophisticated immunological predictors and experimental techniques, several methodological advances have occurred in this field. This review examines contemporary methods to identify and optimize epitopes, engineer their immunogenic properties and develop their safe and efficient delivery into the host.     

Newly recruited intraepithelial Ly6A+CCR9+CD4+ T cells protect against enteric viral infection

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Frame Invariance and Scalability of Neural Operators for Partial Differential Equations

Partial differential equations (PDEs) play a dominant role in the mathematical modeling of many complex dynamical processes. Solving these PDEs often requires prohibitively high computational costs, especially when multiple evaluations must be made for different parameters or conditions. After training, neural operators can provide PDEs solutions significantly faster than traditional PDE solvers. In this work, invariance properties and computational complexity of two neural operators are examined for transport PDE of a scalar quantity. Neural operator based on graph kernel network (GKN) operates on graph-structured data to incorporate nonlocal dependencies. Here we propose a modified formulation of GKN to achieve frame invariance. Vector cloud neural network (VCNN) is an alternate neural operator with embedded frame invariance which operates on point cloud data. GKN-based neural operator demonstrates slightly better predictive performance compared to VCNN. However, GKN requires an excessively high computational cost that increases quadratically with the increasing number of discretized objects as compared to a linear increase for VCNN.     

艾灸治疗原发性痛经作用机制研究进展

艾灸治疗原发性痛经应用广泛,通过热效应、光效应、艾烟及药物作用4种起效机制发挥治疗作用,艾灸治疗原发性痛经的机制集中在调节内分泌激素、调节免疫功能、调节神经相关因素、改善子宫微循环等方面,艾灸治疗原发性痛经的机制研究仍存在问题和不足,应当加强艾灸起效机制研究,重视灸法光效应之中的光谱范围及波峰治疗痛经的机制探索,完善艾灸治疗原发性痛经的机制研究,为临床治疗提供实验依据和循证医学证据。